We intend to determine the general structure and chemical principles governing how proteins interact with and specifically recognize nucleic acids. The major approach will be to crystallize various nucleic acid binding proteins and their complexes with appropriate nucleic acids and to solve their crystal structures by standard protein crystallographic techniques. Appropriate DNA substrates will be chemically synthesized in multimilligram quantities. Mutant DNA's will be synthesized and in vitro protein mutants made, in order to test hypotheses on the source of specificity in protein-nucleic acid interaction that are formulated on the basis of these structures. The proteins that have already been crystallized and on which crystallographic studies are proceeding include E. coli single strand binding protein, the large fragment of DNA polymerase I, and resolvase, which is one of the two essential proteins specified by the GammaDelta transposable element system. In addition we are attempting to crystallize E. coli glutaminyl tRNA synthetase.